The Optimal Cut-off of BIPSS in Differential Diagnosis of ACTH-dependent Cushing's Syndrome: Is Stimulation Necessary?

J Clin Endocrinol Metab. 2020 Apr 1;105(4):dgz194. doi: 10.1210/clinem/dgz194.

Abstract

Contexts: Bilateral inferior petrosal sinus sampling (BIPSS) can differentiate Cushing's disease (CD) and ectopic adrenocorticotropin (ACTH) syndrome (EAS). The traditional cutoff of inferior petrosal sinus to peripheral (IPS:P) ACTH gradient was 2 before stimulation and 3 after stimulation, which yielded unsatisfactory sensitivity in some studies.

Objectives: To determine the optimal cutoff in BIPSS before or after desmopressin stimulation and to evaluate the necessity of stimulation.

Design and setting: Single-center retrospective study (2011-2018) along with meta-analysis.

Patients: 226 CD and 24 EAS patients with confirmed diagnosis who underwent BIPSS with desmopressin stimulation.

Results: In the meta-analysis of 25 studies with 1249 CD and 152 EAS patients, the traditional cutoff yielded sensitivity of 86% and 97% and specificity of 98% and 100% before and after stimulation, respectively. We then analyzed the data from our center. With the traditional cutoff, the sensitivity was 87.2% (197/226) and 96.5% (218/226) before and after stimulation, and specificity was both 100% (25/25), which were close to the results of meta-analysis. Receiver operating characteristic analysis revealed that the optimal cutoff was 1.4 before stimulation and 2.8 after stimulation. With the new cutoff, the sensitivity was 94.7% (214/226) and 97.8% (221/226) while the specificity remained 100% (25/25) before and after stimulation. Among the 7 CD patients (7/226; 3.1%) for whom stimulation was necessary to get correct diagnosis, none has a pituitary lesion >6 mm by magnetic resonance imaging, and their sampling lateralization rate (P = .007) and peak ACTH level at dominant inferior petrosal sinus (P = .011) were lower than those among CD patients with IPS:P >1.4 before stimulation.

Conclusions: The optimal cutoff for IPS:P in BIPSS is different from the commonly-used one. The optimal cutoff value can yield satisfactory accuracy even without stimulation, and stimulation may be unnecessary for those with pituitary adenoma >6 mm.

Keywords: Cushing’s disease; ROC curve; desmopressin; ectopic ACTH syndrome; petrosal sinus sampling.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ACTH Syndrome, Ectopic / diagnosis*
  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Cushing Syndrome / diagnosis*
  • Deamino Arginine Vasopressin / pharmacology*
  • Diagnosis, Differential
  • Female
  • Follow-Up Studies
  • Hemostatics / pharmacology
  • Humans
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Petrosal Sinus Sampling / methods
  • Petrosal Sinus Sampling / standards*
  • Prognosis
  • ROC Curve
  • Retrospective Studies
  • Young Adult

Substances

  • Hemostatics
  • Deamino Arginine Vasopressin